chr15-27126950-G-A

Position:

• chr15-27126950-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033223.5(GABRG3):​c.270+100129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,128 control chromosomes in the GnomAD database, including 6,546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (6546 hom., cov: 32)
• Consequence: GABRG3 NM_033223.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909

Genes affected

GABRG3 (HGNC:4088): (gamma-aminobutyric acid type A receptor subunit gamma3) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. The protein encoded by this gene is a gamma subunit, which contains the benzodiazepine binding site. Two transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Aug 2012]

GABRG3-AS1 (HGNC:40249): (GABRG3 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GABRG3	NM_033223.5	c.270+100129G>A		intron_variant		ENST00000615808.5
GABRG3	NM_001270873.2	c.270+100129G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABRG3	ENST00000615808.5	c.270+100129G>A		intron_variant		1	NM_033223.5	P1
GABRG3-AS1	ENST00000660679.1	n.234-25985C>T		intron_variant, non_coding_transcript_variant
GABRG3	ENST00000555083.5	c.270+100129G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39465 AN: 152010 Hom.: 6548 Cov.: 32

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.0733

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.302

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.259 AC: 39458 AN: 152128 Hom.: 6546 Cov.: 32 AF XY: 0.255 AC XY: 18996 AN XY: 74364

Gnomad4 AFR AF: 0.0666

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.0736

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.300

Alfa AF: 0.346 Hom.: 12542

Bravo AF: 0.250

Asia WGS AF: 0.149 AC: 516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1029937; hg19: chr15-27372097;